Catalyst development for organocatalytic hydrosilylation of aromatic ketones and ketimines

A new family of Lewis basic 2-pyridyl oxazolines have been developed, which can act as efficient organocatalysts for the enantioselective reduction of prochiral aromatic ketones and ketimines with trichlorosilane, a readily available and inexpensive reagent. 1-Isoquinolyl oxazoline, derived from mandelic acid, was identified as the most efficient catalyst of the series, capable of delivering high enantioselectivities in the reduction of both ketones (up to 94% ee) and ketimines (up to 89% ee).     

Evaluation of bifunctional chiral phosphine oxide catalysts for the asymmetric hydrosilylation of ketimines

A series of bifunctional phosphine oxides have been prepared and evaluated as catalysts for the trichlorosilane mediated asymmetric hydrosilylation of ketimines. bis-Phosphine oxides, hydroxy-phosphine oxides, and biaryl phosphine oxides all demonstrated good catalytic activity, but poor to moderate enantioselectivity. A bis-P-chiral phosphine oxide displayed the highest enantioselectivity of 60%.     

Structure investigation of TiIV-BODOLates involved in the catalytic asymmetric reduction of ketones using catecholborane

The complexes formed by the reaction of [Ti(OiPr)(4)] and bicyclo-octanediols (BODOLs) 1 and 2 (1:1) are useful as chiral catalysts in asymmetric reductions and were investigated by (1)H NMR spectroscopy and computational methods. A consistent picture emerged of head-to-tail dimers being kept together via a Ti-O-Ti-O micro-oxo bridge similar to the Ti-tartrates but different from the corresponding Ti-BINOLates and Ti-TADDOLates.     

Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: highly enantioselective synthesis of valuable alcohols

In the presence of PhSiH(3) as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)(2)·H(2)O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting β-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9% enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10,000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98% ee) and exceedingly high turn-over rates (up to 50,000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched β-halo alcohols into the corresponding styrene oxide, β-amino alcohol, and β-azido alcohol, respectively.     

New chiral ruthenium(II) catalysts containing 2,6-bis(4'-(R)-phenyloxazolin-2'-yl)pyridine (Ph-pybox) ligands for highly enantioselective transfer hydrogenation of ketones

Treatment of complex trans-[RuCl(2)(eta(2)-C(2)H(4))[kappa(3)-N,N,N-(R,R)-Ph-pybox]] [(R,R)-Ph-pybox = 2,6-bis[4'-(R)-phenyloxazolin-2'-yl]pyridine] with phosphines or phosphites in dichloromethane at 50 degrees C leads to the formation of novel ruthenium(II)-pybox complexes trans-[RuCl(2)(L)[kappa(3)-N,N,N-(R,R)-Ph-pybox]] [L = PPh(3) (1 a), PPh(2)Me (2 a), PPh(2)(C(3)H(5)) (3 a), PPh(2)(C(4)H(7)) (4 a), PMe(3) (5 a), PiPr(3) (6 a), P(OMe)(3) (7 a) and P(OPh)(3) (8 a)]. Likewise, reaction of trans-[RuCl(2)(eta(2)-C(2)H(4))[kappa(3)-N,N,N-(R,R)-Ph-pybox]] with PPh(3) or PiPr(3) in refluxing methanol leads to the complexes cis-[RuCl(2)(L)(kappa(3)-N,N,N-(R,R)-Ph-pybox] [L = PPh(3) (1 b), PiPr(3) (6 b)]. No trans-cis isomerisation of complexes 1 a-8 a has been observed. Complexes 1 a-8 a, 1 b, 6 b together with the analogous trans-[RuCl(2)[P(OMe)(3)][kappa(3)-N,N,N-(S,S)-iPr-pybox]] (10 a) and the previously reported trans- and cis-[RuCl(2)(PPh(3))[kappa(3)-N,N,N-(S,S)-iPr-pybox]] (9 a and 9 b, respectively) are active catalysts for the transfer hydrogenation of acetophenone in 2-propanol in the presence of NaOH (ketone/cat/NaOH 500:1:6). cis-Ph-pybox derivatives are the most active catalysts. In particular, cis complexes 1 b and 6 b led to almost quantitative conversions in less than 5 min with a high enantioselectivity (up to 95 %). A variety of aromatic ketones have also been reduced to the corresponding secondary alcohols with very high TOF and ee up to 94 %. The overall catalytic performance seems to be a subtle combination of the steric and/or electronic properties both the phosphines and the ketones. A high TOF (27 300 h(-1)) and excellent ee (94 %) have been found for the reduction of 3-bromoacetophenone with catalyst 6 b. Reductions of alkyl ketones also proceed with high and rapid conversions but low enantioselectivities are achieved.